Female genital tract polyps are overgrowths of blood vessels, stroma and glands that can occur in both reproductive and postmenopausal women. Although most are asymptomatic and benign, observational studies report approximately 3.5% of polyps become malignant. There is a lack of research surrounding the common genetic drivers of female genital polyps and the extent to which these polyps cause female reproductive cancers, including endometrial cancer.
We performed a genome-wide association study (GWAS) for female genital polyps using UK Biobank data (ICD10 N84: cases = 13,386, controls = 223,939). Genome-wide risk estimates were meta-analysed with GWAS summary statistics for female genital polyps from FinnGen (freeze 10) resulting in a total GWAS dataset of 29,076 cases and 335,522 controls, the largest such study of female genital polyps to date. After quality control for allele frequency and heterogeneity, we identified 17 genome-wide significant (P < 5 × 10-8) independent genetic loci associated with risk of female genital polyps. The most statistically significant locus was found on 3q21.3, close to the EEFSEC gene which has been implicated in risk of endometrial cancer through genetic analysis. We also identified several loci harbouring genes associated with estrogen signaling, including ESR1 and TRPS1, an estrogen receptor-associated transcriptional repressor. We are currently performing downstream analyses to further our understanding of the genetic underpinnings of female genital polyps, its relationship to cancer development and opportunities for targeted treatment.